title: Human but not mouse adipogenesis is critically dependent on LMO3.
abstract: Increased visceral fat is associated with a high risk of diabetes and metabolic syndrome and is in part caused by excessive glucocorticoids (GCs). However, the molecular mechanisms remain undefined. We now identify the GC-dependent gene LIM domain only 3 (LMO3) as being selectively upregulated in a depot-specific manner in human obese visceral adipose tissue, localizing primarily in the adipocyte fraction. Visceral LMO3 levels were tightly correlated with expression of 11β-hydroxysteroid dehydrogenase type-1 (HSD11B1), the enzyme responsible for local activation of GCs. In early human adipose stromal cell differentiation, GCs induced LMO3 via the GC receptor and a positive feedback mechanism involving 11βHSD1. No such induction was observed in murine adipogenesis. LMO3 overexpression promoted, while silencing of LMO3 suppressed, adipogenesis via regulation of the proadipogenic PPARγ axis. These results establish LMO3 as a regulator of human adipogenesis and could contribute a mechanism resulting in visceral-fat accumulation in obesity due to excess glucocorticoids.
authors.affiliation: Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Josefine
authors.initials: J
authors.lastname: Lindroos
authors.forename: Julia
authors.initials: J
authors.lastname: Husa
authors.forename: Gerfried
authors.initials: G
authors.lastname: Mitterer
authors.forename: Arvand
authors.initials: A
authors.lastname: Haschemi
authors.forename: Sabine
authors.initials: S
authors.lastname: Rauscher
authors.forename: Robert
authors.initials: R
authors.lastname: Haas
authors.forename: Marion
authors.initials: M
authors.lastname: Gröger
authors.forename: Robert
authors.initials: R
authors.lastname: Loewe
authors.forename: Norbert
authors.initials: N
authors.lastname: Kohrgruber
authors.forename: Klaus F
authors.initials: KF
authors.lastname: Schrögendorfer
authors.forename: Gerhard
authors.initials: G
authors.lastname: Prager
authors.forename: Harald
authors.initials: H
authors.lastname: Beck
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Pospisilik
authors.forename: Maximilian
authors.initials: M
authors.lastname: Zeyda
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Stulnig
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Patsch
authors.forename: Oswald
authors.initials: O
authors.lastname: Wagner
authors.forename: Harald
authors.initials: H
authors.lastname: Esterbauer
authors.forename: Martin
authors.initials: M
authors.lastname: Bilban
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000502:physiology; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D017667:Adipocytes / Q000473:pathology; D050156:Adipogenesis / Q000235:genetics / Q000502:physiology*; D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D005938:Glucocorticoids / Q000502:physiology; D006801:Humans; D050152:Intra-Abdominal Fat / Q000473:pathology / Q000502:physiology*; D060588:LIM Domain Proteins / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016513:Mice, SCID; D008875:Middle Aged; D009765:Obesity / Q000473:pathology / Q000503:physiopathology*; D047495:PPAR gamma / Q000502:physiology; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D005938:Glucocorticoids; D060588:LIM Domain Proteins; C502335:LMO3 protein, human; D047495:PPAR gamma; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; C468386:HSD11B1 protein, human